The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding ...sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of Drosophila melanogaster . Unlike in Drosophila , where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the even-skipped gene of the teprhitid Ceratis capitata in transgenic D. melanogaster embryos, six of which drove patterns that recapitulate those of known D. melanogaster enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in D. melanogaster embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify D. melanogaster regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the D. melanogaster genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To determine functional status and mortality rates after colon cancer surgery in older nursing home residents.
Design
Retrospective cohort study.
Setting
Nursing homes in the United ...States.
Participants
Six thousand eight hundred twenty‐two nursing home residents aged 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005.
Measurements
Changes in functional status were assessed before and after surgery using the Minimum Data Set Activity of Daily Living (MDS‐ADL) summary scale, a 28‐point scale in which score increases as functional dependence increases. Regression techniques were used to identify patient characteristics associated with mortality and functional decline 1 year after surgery.
Results
On average, residents who underwent colectomy had a 3.9‐point worsening in MDS‐ADL score at 1 year. One year after surgery, rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (≥80 vs 65–69, adjusted relative risk (ARR) = 1.53, 95% confidence interval (CI) = 1.15–2.04, P < .001), readmission after surgical hospitalization (ARR = 1.15, 95% CI = 1.03–1.29, P = .02), surgical complications (ARR = 1.11, 95% CI = 1.02–1.21, P = .01), and functional decline before surgery (ARR = 1.21, 95% CI = 1.11–1.32, P < .001) were associated with functional decline at 1 year.
Conclusion
Mortality and sustained functional decline are common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population.
IMPORTANCE: Lower extremity revascularization often seeks to allow patients with peripheral arterial disease to maintain the ability to walk, a key aspect of functional independence. Surgical ...outcomes in patients with high levels of functional dependence are poorly understood. OBJECTIVE: To determine functional status trajectories, changes in ambulatory status, and survival after lower extremity revascularization in nursing home residents. DESIGN: Using full Medicare claims data for 2005 to 2009, we identified nursing home residents who underwent lower extremity revascularization. With the Minimum Data Set for Nursing Homes activities of daily living summary score, we examined changes in their ambulatory and functional status after surgery. We identified patient and surgery characteristics associated with a composite measure of clinical and functional failure—death or nonambulatory status 1 year after surgery. SETTING: All nursing homes in the United States participating in Medicare or Medicaid. PARTICIPANTS: Nursing home residents who underwent lower extremity revascularization. MAIN OUTCOMES AND MEASURES: Functional status, ambulatory status, and death. RESULTS: During the study period, 10 784 long-term nursing home residents underwent lower extremity revascularization. Prior to surgery, 75% of the residents were not walking; 40% had experienced functional decline. One year after surgery, 51% of patients had died, 28% were nonambulatory, and 32% had sustained functional decline. Among 1672 residents who were ambulatory before surgery, 63% had died or were nonambulatory at 1 year; among 7188 who were nonambulatory, 89% had died or were nonambulatory. After multivariate adjustment, factors independently associated with death or nonambulatory status were 80 years or older (adjusted hazard ratio AHR, 1.28; 95% CI, 1.16-1.40), cognitive impairment (AHR, 1.23; 95% CI, 1.18-1.29), congestive heart failure (AHR, 1.16; 95% CI, 1.11-1.22), renal failure (AHR, 1.09; 95% CI, 1.04-1.14), emergent surgery (AHR, 1.29; 95% CI, 1.23-1.35), nonambulatory status before surgery (AHR, 1.88; 95% CI, 1.78-1.99), and decline in activities of daily living before surgery (AHR, 1.23; 95% CI, 1.18-1.28). CONCLUSIONS AND RELEVANCE: Of nursing home residents in the United States who undergo lower extremity revascularization, few are alive and ambulatory 1 year after surgery. Most who were still alive had gained little, if any, function.
...the blocks themselves cover only a small fraction of the bases in the enhancer. Conclusion A careful analysis of sepsid and Drosophila even-skipped enhancers reveals changes in the organization ...of transcription factor binding sites that are not compatible with a model in which conserved expression patterns are generated by a single conserved binding site organization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk
. ...However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common
and is most severe in the very young
, in whom it can be life threatening and difficult to treat
. Autoantibody surveillance programs effectively prevent most ketoacidosis
but require frequent evaluations whose expense limits public health adoption
. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible
because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.
We discuss the experience of some Pacific island countries in introducing the new WHO-recommended treatment protocol for lymphatic filariasis-a triple-drug therapy composed of ivermectin, ...diethylcarbamazine, and albendazole. The successful rollout of the new treatment protocol was dependent on strong partnerships among these countries' ministries of health, WHO, and other stakeholders. Effective communication among these partners allowed for lessons learned to cross borders and have a positive impact on the experiences of other countries. We also describe various challenges confronted during this process and the ways these countries overcame them.
BackgroundHuman studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on ...outcomes.MethodsSixty preterm neonates <32 weeks gestational age with magnetic resonance imaging (MRI) scanning at near-birth and near-term age were assessed for brain tissue volumes, including cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and ventricular cerebrospinal fluid. Red blood cell fatty acid content was evaluated within 1 week of each MRI scan. Neurodevelopmental outcome at 30-36 months corrected age was assessed.ResultsAdjusting for potential confounders, higher near-birth docosahexaenoic acid levels are associated with larger cortical gray matter, deep gray matter, and brainstem volumes and higher near-term levels with larger deep gray matter, cerebellar, and brainstem volumes at near-term age; lower near-birth linoleic acid levels are correlated with larger white matter volume at near-term age. By 30-36 months corrected age, larger cortical and deep gray matter, cerebellar, and brainstem volumes by term age are associated with improved language scores and larger cerebellar and brainstem volumes with improved motor scores.ConclusionSpecific polyunsaturated fatty acid levels have differential and time-dependent associations with brain region growth. Larger brain volumes are associated with improved outcomes at preschool age.
We describe the process converting half of our 40-bed PICU into a negative-pressure biocontainment ICU dedicated to adult coronavirus disease 2019 patients within a 1,003-bed academic quaternary ...hospital. We outline the construction, logistics, supplies, provider education, staffing, and operations. We share lessons learned of working with a predominantly pediatric staff blended with adult expertise staff while maintaining elements of family-centered care typical of pediatric critical care medicine. Critically ill coronavirus disease 2019 adult patients may be cared for in a PICU and care may be augmented by implementing elements of holistic, family-centered PICU practice.
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